In normal physiology the Tau protein promotes microtubule assembly and stability and is critical for the function of axons. However, Tau has been identified in a highly phosphorylated form as the filamentous core of the neurofibrillary tangles (NFT) or insoluble tau aggregates. Accumulation of NFTs or other inclusions containing Tau in the brain are histopathological features of many neurodegenerative diseases, which are collectively known as tauopathies. Tauopathies include, e.g., Alzheimer's disease (AD), Pick's disease (PiD), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and frontotemporal lobar degeneration (FTLD).
It is predicted that about half of the estimated one billion people over the age of 65 in 2050 will have some Tau inclusions (e.g., neurofibrillary tangles (NFT)) in their brains.
The best-known tauopathy is Alzheimer's disease (AD), where the Tau protein is deposited within neurons in the form of neurofibrillary tangles (NFTs). Tangles are formed by hyperphosphorylation of Tau, causing it to aggregate in an insoluble form. These aggregations of hyperphosphorylated tau protein are also referred to as PHF, or “paired helical filaments”.
There is a large and rapidly growing unmet need for disease modifying drugs for Alzheimer's disease (AD) and other tauopathies.
The molecular interactions that underlie the formation of neurofibrillary tangles (NFT) or insoluble tau aggregates are presently unknown.
There is a need for assays and related methods for identifying compounds that are likely to inhibit the pathological function of Tau, such as the formation of neurofibrillary tangles.
Reference to any prior art in the specification is not, and should not be taken as, an acknowledgment or any form of suggestion that this prior art forms part of the common general knowledge in Australia or any other jurisdiction or that this prior art could reasonably be expected to be ascertained, understood and regarded as relevant by a person skilled in the art.